Committed to Excellence in Cancer Research, Education and Patient Care
Inroads
November 2023
Researcher Studies Role of 'Cellular Post Office'
in Lung Cancer Growth & Metastasis
Xiaochao Tan, PhD, Assistant Professor of Hematology & Medical Oncology, explores the role of the Golgi apparatus in lung cancer initiation, growth and metastasis.
Vector illustration on Lung Cancer awareness month in November.
Tulane Cancer Center recently welcomed Xiaochao Tan, PhD, whose research focuses on the role of the Golgi apparatus – an organelle or subunit found in the cytoplasm of cells – in lung cancer growth and metastasis.
 
The function of the Golgi apparatus – often referred to as the "post office of the cell" – is to package proteins for delivery to other sites both within and outside of the cell, where they carry out specific biological functions. The proteins are synthesized within the cell and then transported to the Golgi apparatus, where they are loaded into fatty containers called vesicles which essentially function as "mail trucks", delivering the proteins to other organelles within the cell, to the cell membrane or to the extracellular matrix.
 
Lung cancer tumors have found a way to hijack this process and reprogram the Golgi apparatus to increase pro-tumor protein secretion. "Dysregulation of the Golgi apparatus has emerged as a significant factor driving the initiation and progression of lung cancer," said Tan, assistant professor of medicine in the Section of Hematology and Medical Oncology.
 
Through his research, Tan has identified several Golgi apparatus proteins that are amplified in lung tumor cells and has hypothesized that they could be potential drivers of lung cancer progression. "These Golgi proteins are not mutated, but their expression is increased in the tumor cells," said Tan. "The tumor cells appear to use a positive feedback loop to stimulate the secretory pathway to generate or 'bud' more pro-tumor protein-filled vesicles. The secreted proteins find receptors on the tumor cell membrane which then activate pathways to promote additional Golgi secretion, a circular process that supports tumor cell growth and metastasis."
 
Tan and his team have also investigated the role of amplified Golgi genes in cancer initiation and progression. "There are regions on the Golgi chromosomes that are broken, duplicated or amplified in tumors with a high expression of Golgi proteins," said Tan. A deeper understanding of these oncogenic processes could ultimately contribute to the development of innovative therapeutic approaches for lung cancer.
 
Some researchers have attempted in clinical trials to thwart the tumor-driving action of secreted proteins by using neutralizing antibodies or decoy receptors, but they have been largely unsuccessful. "Because the tumor cells find ways to compensate," said Tan. "If you inhibit one secretory protein, another one can play the same function. We need to find a therapeutic approach that targets the whole secretion process. If we shut down secretion, then the cancer cells can no longer get the proteins they need for growth and metastasis."
 
Towards that end, Tan and his team have identified and targeted a key regulator of secretion, an enzyme called PI4KIIIβ that drives protein packaging and vesicle formation in the Golgi. His group previously tested the anti-tumor activity of drugs that inhibit PI4KIIIβ – drugs that coincidentally were being developed as anti-viral agents for viruses such as hepatitis and Ebola – and found they also kill lung cancer cells with specific genetic mutations. These data plus additional testing in animal models will provide a foundation for clinical trials utilizing PI4KIIIβ inhibitors to shut down pro-tumor protein secretion in lung cancer.
Robotic Bronchoscopy Program Helping Detect Lung Cancer Earlier Than Ever Before
Dr. Ramsy Abdelghani utilizes real-time cone beam CT scan imaging to help guide a robotic bronchoscope directly to a small nodule in a patient's lung.
"Think of a large oak tree with a huge trunk and hundreds of branches," said Ramsy Abdelghani, MD, director of Tulane's Interventional Pulmonology Program, "and I'm being guided to one specific leaf."

That's how he describes the capabilities of Tulane's state-of-the-art Robotic Bronchoscopy Program, which combines a robotic bronchoscope with real-time advanced cone beam CT scan imaging, allowing him to precisely navigate to virtually anywhere within the lungs and biopsy smaller lesions than ever before. This leads to earlier diagnoses of lung cancer, essential for good outcomes. Tulane has performed more of these advanced procedures than any other program in the state.

The robot utilizes a pre-procedural CT scan to precisely isolate the location of the nodule and create a suggested route for the bronchoscope — GPS-like directions that allow Abdelghani to guide a thin, 360-degree maneuverable catheter through the numerous airways that make up the lungs directly to his target. And some of these nodules are as small as 3.5 mm in diameter — approximately three times smaller than those he could biopsy previously.

"I use a console to drive the robot, almost like a video game," said Abdelghani. "Without guidance, this would be extremely challenging. These airways all look the same and there are hundreds of wrong turns I could make along the way."

Once the target is reached, a low-dose CT scan allows Abdelghani to see the spatial relationship of the catheter to the nodule, make adjustments if necessary and then biopsy with confidence that he's in the correct position to retrieve a good tissue sample. "If the pathology comes back benign, I can say with relative certainty that I got a good representation of the lesion," said Abdelghani. "The way I think about it is the robot gets me to the driveway, but the cone beam CT scan gets me to the front door."

All Tulane Medical Center patients with lung nodules are now referred to Abdelghani's clinic. Previously, small lung nodules that incidentally showed up on imaging tests of the heart or abdomen may not have been candidates for biopsy because they were too small. "But since the availability of robotic bronchoscopy, I haven't said no yet," said Abdelghani, who has biopsied approximately 250 nodules in the year since the program started.

Robotic bronchoscopy requires general anesthesia. However, the potential risks of this scarless, well-tolerated, virtually pain-free procedure are quite low, and Abdelghani says most patients go home the same day.

If you are interested in learning more or making an appointment with one of Tulane's board-certified interventional pulmonologists, please contact Abdelghani at rabdelgh@tulane.edu or call Tulane's Lung Nodule Clinic at 504-988-8600.
New ACS Lung Cancer Screening Guideline Increases Eligibility
The updated ACS guideline recommends adults aged 50-80 who have a 20+ pack-year smoking history get screened with a low-dose CT scan each year. (Story and photo from the ACS).

The new lung cancer screening guideline, published in the ACS flagship journal, CA: A Cancer Journal for Clinicians, recommends that primary care or specialty care providers refer those between the ages of 50 to 80 for yearly screening with LDCT if they


People should not be screened if they have serious health problems that will likely limit how long they will live, or if they won’t be able to or won’t want to get treatment if lung cancer is found.

The guideline also calls for health care providers to have a shared decision-making conversation that explains that the leading organizations agree on the value of lung cancer screening and includes the benefits, limitations, and harms of screening with LDCT, smoking-cessation counseling, and other available interventions to help people who are currently smoking to quit.

This guideline aims to reduce the number of deaths from lung cancer. Each year, more people in the United States die from lung cancer than from colon, breast and prostate cancers combined. If lung cancer is found at an earlier stage, when it’s small and before it has spread, it’s more likely to be treated successfully.

These changes in the guideline mean that nearly 5 million more people will be eligible for lung cancer screening each year:

  • People aged 50 to 80 years who currently or formerly smoked should talk with a health care provider about lung cancer screening. (Previously, the ACS guideline was ages 55 to 74 years.)
  • People with lower pack-year histories qualify for screening. The new guideline recommends screening for anyone with a 20+ pack-year history. (Previously, the ACS guideline included a 30+ year pack history).
  • The most important change in the updated guideline is that the number of years since quitting smoking is no longer a qualifier for starting or stopping yearly screening. That means a person who used to smoke with at least a 20 pack-year history, whether they quit yesterday or 20 years ago, is considered to have a high risk for developing lung cancer and should be recommended for a yearly LDCT scan if they don't have a serious health problem that will likely limit how long they will live, or if they won’t be able to or won’t want to get treatment if lung cancer is found. (Previously, the ACS guideline recommended only people who had quit 15 years ago or less.)

These changes mean that many people who started screening will not lose eligibility by reaching 15 years since they quit. This is important because their risk of lung cancer is still rising due to increasing age. 

The last change also means those who have a 20+ pack-year history and reach their 15th year since quitting before age 50 will now be eligible to start and continue screening. 

The new lung cancer screening guideline also emphasizes the importance of shared decision-making about screening and counseling to help people quit using cigarettes.

“The number one reason people give for not getting a lung cancer screening test is that their health care provider didn’t talk to them about it at all, or didn’t talk to them thoroughly,” says Robert Smith, PhD, the Sr. Vice President for Early Cancer Detection Science at ACS.

Interestingly, studies have shown that other methods—including video and online educational interventions, pre- and post-intervention surveys, and using decision aids on a patient portal—were not as effective as an empathetic, comprehensive conversation with a health care professional.

“Studies show that screening behavior is more nuanced than a provider making a simple recommendation,” the guideline authors say. “Rather, the quality and content of the communication around the recommendation are significant and have an important influence on a patient’s decision to get screened.”

The guideline calls for shared decision-making between patients and a qualified health professional. Additionally, the Centers for Medicare and Medicaid Services (CMS) require shared decision-making as part of counseling before referring Medicare beneficiaries for screening.

This update aligns with recently updated recommendations for annual lung cancer screening from the US Preventive Services Task Force (USPSTF), the American Academy of Family Physicians (AAFP), the National Comprehensive Cancer Network, and the American College of Chest Physicians.
close up man hand holding peel it off cigarette pack prepare smoking a cigarette. Packing line up. photo filters Natural light.
What's Pack-Year History?

Pack-year history describes how long a person smoked traditional, combustible cigarettes and how many packs were smoked. One pack contains 20 cigarettes. To calculate the number of pack years, multiply the number of years a person smoked by the number of packs they smoked each day. 

The new ACS lung cancer screening guideline says anyone with a 20-pack-year history or more qualifies for getting a yearly low-dose CT scan to screen for lung cancer. A person could have a 20-pack-year history, for example, if they smoked:

  • 1 pack a day for 20 years
  • 2 packs a day for 10 years
  • 1 ½ packs a day for a little longer than 13 years
  • 3 packs a day for a little longer than 6 ½ years
Tulane's Low-Dose CT Lung Screening
Saves Lives
Tulane's low-dose CT lung cancer screenings can help detect lung cancers at their earliest stages, when they are most treatable.
 
"The earlier you find the cancer, the better the prognosis," said Mark Sides, MD, PhD, head of Tulane's Thoracic Oncology Program. "This screening can save your life. Five-year survival rates go down dramatically with each stage of the disease. If we can catch stage 1 –when lung cancer is typically asymptomatic –then it's a surgical issue. The surgeon goes in, removes the tumor and the patient is cured."
 
This non-invasive, painless test only takes a few minutes. Radiation exposure from low-dose CT is slightly more than an x-ray but less than 10% of the radiation from a standard CT scan.

"Anything actionable will be picked up with much less radiation," said Dr. Sides. "If a detected lesion is below a certain size, we simply watch it, do serial screenings, and if it doesn't change, it doesn't change. It's very unlikely it's cancer."

Most insurance providers cover low-dose CT lung cancer screening for patients who meet the screening eligibility criteria. Please check with your insurance provider to confirm screening coverage.

A CT scan requires a physician's order. If you are interested in a low-dose CT screening, please call 504-988-6509 or have your doctor call with a referral.
The American Cancer Society Has Tools & Resources to Help You Quit Smoking
Close up portrait of young attractive woman breaking down cigarette to pieces. Studio shot selective focus isolated on grey. Addiction concept
About 34 million American adults still smoke cigarettes, and smoking remains the single largest preventable cause of death and illness in the world. Smoking causes an estimated 480,000 deaths every year, or about 1 in 5 deaths.

While the rates of cigarette smoking have declined over the past several decades, from 42% in 1965 to 14% in 2019, the gains have been inconsistent. Some groups smoke more heavily or at higher rates and suffer disproportionately from smoking-related cancer and other diseases. These populations tend to be those who experience inequities in multiple areas of their lives, including those at lower socioeconomic levels, those without college degrees, American Indians/Alaska natives, African American/Black communities, LGBTQ communities, those in the military, those with behavioral health conditions, and others. 

No matter your age or how long you’ve been smoking, quitting improves health both immediately and over the long term. Quitting smoking is a process, and success may look different for different people. There are many ways to quit smoking, and some work better than others. The American Cancer Society can tell you about the steps you can take to quit smoking and help you find quit-smoking programs, resources, and support that can increase your chances of quitting successfully. To learn about the available tools, call them at 1-800-227-2345.
Save The Date:
Cancer Crusaders Mardi Gras BINGO BASH
Winner poster with lottery balls with numbers_ confetti and golden bingo. Realistic lotto game big win background. Gambling vector concept. Illustration of winner lottery_ game gambling
Mark your calendars! You won't want to miss the Cancer Crusaders Mardi Gras Bingo Bash, being held at Chateau Golf & Country Club, 3600 Chateau Blvd., Kenner, on Tuesday, February 6, 2024.

In addition to bingo, this fun and festive cancer research fundraiser features lunch, a cash bar, and higher-end raffles. And, of course, no Mardi Gras-themed event would be complete without a costume contest! SO, get your tickets right away and start planning your winning ensemble.

Bingo Bash tickets cost $60 each and are available online here beginning at 2 p.m. on December 5. But get yours early! They only have seating for 300 guests and this event sold out quickly last year.

Sponsorships are available for $1,000 each, providing the first 10 seats at a premium table.

Cancer Crusaders is a local non-profit, all volunteer organization that has been raising funds for cancer research in the New Orleans area since 1976. Believing fervidly in their motto – The Answer to Cancer is Research – this group hosts several fundraisers in addition to the Bingo Bash each year – the Cancer Crusaders Golf Tournament; the Seersucker & Sass Summer Gala; and their signature event, the Annual Celebration of Life Luncheon, which honors local cancer survivors who are making a difference in the community.

Since their founding, the organization has raised over $4.4 million, which has been split equally between the cancer research programs at Tulane and LSU.

Join them at the Bingo Bash – or any of their other amazing events – and help them to continue making a difference in the search for cures.